Translational GTPase (trGTPase)

Translational GTPases (trGTPases) are a superfamily of enzymes that are essential for the accuracy and efficiency of protein synthesis across all domains of life [Atkinson, 2015]. These proteins, which include Elongation Factor G (EF-G), Elongation Factor Tu (EF-Tu), and Initiation Factor 2 (IF2), bind to the ribosome and utilize the energy from GTP hydrolysis to drive the mechanical steps of translation [Maracci & Rodnina, 2016]. By cycling between GTP-bound active and GDP-bound inactive states, they coordinate the recruitment of tRNAs, the movement of the mRNA-tRNA complex, and the release of the finished polypeptide [UniProt]. In clinical practice, bacterial trGTPases are the primary targets for several classes of antibiotics, such as fusidic acid, which traps EF-G on the ribosome to halt protein production [DrugBank]. In humans, dysregulation of eukaryotic counterparts like eEF2 is associated with oncogenesis and neurodegeneration, making them targets for toxins and potential small-molecule inhibitors [PubMed]. Despite their therapeutic potential, the high degree of conservation between bacterial and mitochondrial GTPases presents a significant challenge for avoiding host toxicity [PubMed].

Other names

Ribosome-dependent GTPasetrGTPaseTranslation factor GTPaseRibosome-associated GTPase

Inhibition of GTP hydrolysis, stabilization of the factor-ribosome complex to prevent dissociation, or blocking of the factor binding site on the ribosome.